as every geneticist can tell you, reducing the genetic diversity of a population is the path of maximum idiocy.
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I assure you the goals of genetics and the agenda the Nazis are one and the same.

Genetics research is simply Hitler by committee. Sticking a needle into the womb of a pregnant woman to suck out the DNA of an unborn child is a dead giveaway.

Don't let the UK GMC catch you doing that. They'll go bonkers, right?

Milo;
Thanks for explaining it to me. That is was only the one! And even then it really was not serious and all.

But since I am paranoid (for very good, sound, logical reasons) one is more than enough, and paranoid me wonders what else is there under the rocks that just did not get turned over into the light of day. Just saying!

@John Stone

Let's make this dirt simple.

176 people were involved in performing a study. Two have minor conflicts, which they have stated. For the rest of them, you have not identified any conflicts of interest.

One of the senior authors holds a chair which is named after GSK. He receives no funds from GSK. He did not state a conflict of interest, since he has none.

You have written a paper in which you try very hard to imply that the study is somehow bogus, irrelevant, or tainted because of this. You directly imply that 176 scientists sold their integrity and followed a false genetic trail (instead of data that is so clear, any number of laypeople can see it from a mile away), therefore endangering countless children.

They did all of this because one of them has a chair named after a pharma company.

This is not right. You can argue with me about my opinion of percentage of autism that is genetic, but that is a separate subject. The main point is that you attack people who work on Autism Genome based on a completely imaginary conflict of interest.

Furthermore, ICMJE rules would not require that Scherer report imaginary conflicts of interest. No rules do. Under ICMJE rules, he still wouldn't have to report the name of his position, as it is completely irrelevant.

(I give a donation to university. University names a chair in my honor. Twenty years later, the professor who holds that chair has to report that as a conflict on interest, even though he has nothing to do with me? I'm sorry, but that is untenable.)

You can dance around this issue all you want, but your conduct in this article is just simply wrong.

As for usefulness, this study is of critical importance for figuring out autism. Discovering the pathways involved is the only way to any treatment. Your opinion may differ, and you are free to write that - go ahead, write an article on how this study is useless (in your opinion). But don't make up nonexistent conflicts of interest, and use that to imply corruption of people you don't even know.

Finally, as for weight of my criticism, this is a blog comment open to the public. If you don't want to attach any weight to it, then don't. I don't share my information lightly, but Milos is my real name, and it is rare enough among neuroscientists that you can find me rather easily if you want to. You can, again, interpret that as you will.

If you want genetics research this "genetics" study and all the rest are just another part of the CDC anti-litigation bloc of Autism research.

Those who say "prove it" actually mean "just try to convince me."

Probably the most overhyped and mis-spun non-result in the whole of history. Why accuse authors of corruption when their own paper betrays the fact that they have failed to find any major cause of autism (indeed any cause of real autism at all)... http://www.autismcauses.info/2010/06/copy-number-variations-are-only.html

Milos

1) I have already pointed out one criterion on which Prof Scherer - and as you further point out members - of his department should have disclosed this: even if GSK's political and financial involvement with the department was substantially in the past they would still be beneficiaries of corporate largesse, but we don't know that it is over at all. Your theory (unsubstantiated) is that they just wanted their name advertised (in which case Prof Scherer would be a walking advertisement).

2) The disclosures are woefully incomplete on the paper - as I pointed out at the beginning - including authors that have given evidence on behalf of pharmaceuatical companies in autism cases. 176 authors, two lines of disclosures: this is not credible.

3) This would not have been possible under ICMJE rules.

4) You made a false claim before about more than 40% of autism being genetic, which you can't substantiate and is altogether fanciful - and now don't defend it.

5) If there were infinite resources I might support this study but I don't think it is finding anything useful or promising and it doesn't offer anything to help the children - it is simply a speculative activity which wastes resources and diverts public attention:

http://www.telegraph.co.uk/science/steve-jones/5189941/One-gene-will-not-reveal-all-lifes-secrets.html

6) I don't give a lot of weight to people like you who parade their expertise, integrity and their false anger but cannot actually say who they are.

Milos
We are all paranoid!

John,

1) There is no association between Professor Scherer and GSK. He receives no money from them. He is not beholden to them. He has nothing to declare.

2) I don't know if you were confused, but your entire article attempts to insinuate that because one senior author has an endowed chair which has GSK in its name, the study is somehow corrupted, or was done for nefarious purposes.

Let me be perfectly blunt.

Like many other scientists, I have chosen a poorly-paid academic career over pharma industry (I have had offers that would triple my pay). This is not that uncommon of a choice: independence and meaning over money.

If I had an inkling - a barest inkling - that a pharma company was endangering the lives of children, I would fire from all available barrels. Pretty much all of my colleagues would do the same.

Yet, you and many people on this blog believe (unshakeably) that we are all either blind idiots, or we are laughing all the way to the bank with bags of pharma money over our shoulders.

This is deeply insulting.

You have, in this article, based on nothing but the NAME of an ENDOWED CHAIR, besmirched the reputation of over a hundred hard working, dedicated people, who are spending their lives trying to figure out the roots of the disease that affects so many.

You should support this study. Ok, fine, unlike anyone in the field you believe that vaccines cause autism. You could interpret the study as "identifying genes that make children susceptible to vaccine injury", and try to make sense of results in that light.

But no. Instead you have chosen to insult the entire field. Again.

3) No single CNV correlation is dramatic, this is true. But data like this is sorely needed to make sense of what makes children vulnerable, and can help us predict where to focus our future efforts.

4) Known genetic syndromes (many of them metabolic) account firmly for 20% of autism cases. There is high confidence for at least another 20%, just based on heritability studies alone. This is before we even start talking about copy number variants.

But this is beside the point. The main point is #2 above.

The paper states that a little over 4% of ASD cases have rare CNV (copy number variants) in a group of 996 ASD cases, whereas a little over 2% of controls have them in a group of 1287 controls. They have looked at three primary measures of CNV burdens: the number of CNVs per individuals, the estimated CNV sizes and the number of genes affected by CNVs. No differences are found in the former two. By contrast it is stated there is a significant increase in the number of genes intersected by rare CNV in ASD cases when focusing on gene-containing segments.

When they look at 103 ASD candidate genes they found no statistical difference in the percentages of samples with rare CNVs between ASD and controls. When they narrow their list of genes to 36 genes, claimed to be implicated as disease gene in ASD, they find a statistical difference between the 2 groups. In other words, they have to select both individuals and gene areas to obtain a statistical difference between ASD and controls.

More importantly still, we are only talking overall at most of 2% of the ASD sample who have these CNVs above that of the control group (2% is about the difference between ASD and control). This is an excessively low percentage.

I note that in the introduction, it is stated that “Some 5-15% of individuals with an ASD have an identifiable genetic aetiology corresponding to known single-gene disorders (for example, fragile X syndrome) and chromosomal rearrangement (for example, maternal duplication of 15q11-q13). There is no reference attached to this statement. This statement is totally at odd with our own observations in a group of 400 ASD children. In this sample, 3 children only, that is less than 1% have a known genetic condition. One has Fragile X, one has NF-1 and the other has a partial trisomy of chromosome 15. Note that in the mid 80s about 8% of the ASD population had a known mutation with Fragile X. The representation of this genetic condition in the current ASD population is much reduced. This indicates that the increased cases of autism are not related to better diagnosis of “genetic ASD”. Indeed, if this was the case, we would still have 8% about of the current ASD population presenting with Fragile X. What it tells us, is that we have a new population of children currently being diagnosed as ASD with additional novel environmental triggers implicated. Admittedly these children might not have ASD, but something else presenting as ASD.

Somewhere else in the paper, it is stated “ Single-occurrence CNV deletions had increased rates in ASD cases over controls, indicating that some could be pathogenic”. Such statement is a pure assumption, only when a genetic change is being recreated in an animal model, and a pathology consistent to that of autism is caused, can a direct implication be demonstrated. Any geneticist knows it is the case. An association does not prove causality.

It is also stated that 5.7% of ASD cases have at least one de novo CNV, meaning it was not present in the parents, but somehow there is no tentative explanation as to why that may be. Higher rate of mutation relates to an environmental causality, should this be a concern? I do not imply that these mutations are related to their autism, but surely, if the genetic material in some ASD children presents with higher levels of de novo changes, we have to be concerned about the implications behind this.

Thanks John! And thank you Natasa! Couldn't have said it better myself. These "huge gene breakthroughs" are not breakthroughs in the least. The public has to be confused considering every 3 or so months the "New" mysterious genes in autism have been found (always different than the ones previously reported on) but then in a quick mention at the end of the report it's mentioned they've only found them in tiny percentages of the ASD population and the reports always fail to mention that the same mutations, deletions, duplications, etc are found in much of the control cohorts as well. Smoke and mirrors....

To Esa, Milos etc:

of oourse genetics has a lot to do with autism. In the same way that genetics has a lot to do with sneezing!! Or anything else in a living being for that matter. Every time you sneeze it is the reflection of genetically predetermined reaction to your requirement. Every blink of an eye is genetically predetermined reaction to whatever.

Most of those gene studies listed on pubmed that you mention are not worth the paper they are written on, or the screen pixels. Not in terms of not finding sequences etc but in terms that they do not contribute much to to anything, really.

What those genetic "breakthrough" studies often fail to disclose in their press release, and often have buried deep inside their papers in a very muddled-hard-to-find way, is that those mutations are ALWAYS found in a LARGE number of healthy children/adults.

So two things really:

1. NOT ONE of those 'genetic' linkage studies has come across any single gene, or any combination of genes, that are not present in healthy population. Meaning that not one of those mutations or those combinations “causes” autism.
2. even if it did, it would account for a minute percentage of affected individuals

This latest sharade of a study, the Pinto/Sherer one, found the “breakthrough” CNVs in a whopping 5.something percent of ASD children. You tell me in what percentages did those CNVs pop in the healthy controls? Please?! Then let us know the difference, and how it could account for anything approaching useful.

Btw that often quoted line of 10-15% of autism has a genetic basis is based on nothing really and are a self-perpetuating myth. The percentages are plucked from thin air. If we consider monogenetic disorders such as fragileX, Downs Syndrome etc, those put together will account for much much less than even 5% percent of cases today.

The Emperor has no clothes. He has been naked all along. Those who fund these expensive useless studies seem to be completely blind.

The order of authors listed on scientific publications is almost always in decreasing order of intellectual contribution to the project.

The first author on this paper is the one who had the most say in the design and execution of this project and probably the person who spent the most hours slaving at the bench with a micropippette.

In most big labs (including the one I work in) the PI (the faculty member who runs the lab--listed as "senior author") is often so busy with overseeing all of his other projects that his role is almost purely advisory. For example, in the last paper I published, my PI has ABSOLUTELY NO CLUE what it's about--simply because my project is so peripherally related to most of the other research going on in the lab. In spite of this, he is still listed as the "senior author" on that paper.

The money from the GSK endowment is controlled by Sherer and his University...not GSK. GSK has absolutely NO SAY in what sort of research that money is spent on--it is in the hands of the department and faculty to decide that.

There is a lot of good, hard, evidence supporting a combination of genetic and environmental factors as the major underlying causative agents of autism spectrum disorders. Simply go to pubmed central and do a search for "autism genetics" and you will literally find hundreds of peer-reviewed papers supporting a genetic cause.

For a more condensed summary of the research that's been done so far visit the OMIM page on autism (link provided below)

http://www.ncbi.nlm.nih.gov/omim/209850

"Lexington Herald Leader" had an article from the "New York Times" by Nicholas Wade.

"A decade later, gene map yields few new cures"
The hunam genome was complete 10 years ago, and medicine has yet to see any large benefits. The goal of Human Genome Project was to sequence three billion chemical units in the gentic instruction trying to find the genetic roots of diseaes,and then developing treatments. With the human genome sequence finished they set about trying to find the variants that increase the risk of disease. Our beloved National Institues of Health embraced the idea for a clever shortcut since it was far too expensive to sequence patients' whole genomes. They looked at the genome where many people have a variant DNA unit. But nothing is being found. Ha!

But, still the National Institue of Health with a stiff upper lip, is not giving up. Now they are going to see if any of the variants are more common in patients with a given diseae than in healthy people. These studies required large numbers of patients and cost several million dollars apiece! So there is our money.

The question often raised when I was majoring in biology was which is more important the environment or the genes. Looks like it is the environment.

They are desperate. How pathetic. Truly embarassed for these sell outs.

Re: Dalila Pinto (U. of Toronto) being the "first author", if you go to the Nature article link http://www.nature.com/nature/journal/vaop/ncurrent/full/nature09146.html - there are two others right after her also non-alphabetical - Alistair T. Pagnamenta (U. of Oxford) & Lambertus Klei (U. of Pittsburgh) - after that it is strictly alphabetical.

Pinto's the grad student and/or post doc writing this (and Pagnamenta and Klei obviously had a big hand in writing/analyzing the data as well). Note: I love the fact that Szatmari doesn't have a graduate student intimately involved.

This is Scherer's staff:
http://www.tcag.ca/staff.html

In this situation he'll direct - but each graduate student/post doc/whatever will be the lead author of whatever paper. His lab will have many, many papers going at once, in one of the following forms: proposed, studied, in draft form, being submitted, being reviewed, being edited again (to address any questions of the reviewers), being published. He'll have a hand in writing/editing anything coming out of his lab (as he is directing it) - but, the particular graduate student/post doc whose area of research is - this or that - will be the lead author. This is standard - and not a mystery. If he did anything else (took top authorship), it would be unseemly. This is one of the few perks a grad student/post doc have - and it is a way of acknowledging their contribution - as they did the bulk of the analysis (under direction).

Theresa O. - My thoughts exactly.

Geri Dawson, by the way, is listed as a co-author of the paper.

I need an expert geneticist to tell me the history of discovering the gene for sickle cell anemia for example, and a host of other inherited maladies. It seems to me that these are a very finite discovery and any pregnancy can be "genetically tested" through a sample of amniotic fluid for any number of possible inherited conditions. Finding a gene for autism should be just as "easy" as how we found those others, shouldn't it? Anyone know more about those?

And if finding a gene for autism does not line up with the history of how we found the link to other conditions, then at what point can we abandon the search?

Not so much as an "Oops!" from Mr. Scherer?

Im increasingly interested in the human DNA present in the Rubella that was presented by Dr Deisher at the INSAR meeting....

could the human DNA from the aborted fetus be a factor on the gene variations? Im becoming more convinced because the DNA present from vial to vial is so GREATLY varied- that would explain why "some" kids are more susceptible than others...

her studies so far arent funded by pharma =)

I am embarrased that such a stupid study has come from Canada. So John, is this Nature journal sketch?

Wow, that's a lot of "disease genes"! Why have they become such a problem suddenly? A special ed art teacher I talked to a while ago speculated that it was mixing of genes between populations that was causing the autism epidemic. Is that where this is going?

She also mentioned that every autistic kid she'd ever taught had bowel problems.

Are we surprised John - surely this is just another example of the protectionist stance GSK and other purveyors of these damaging products, that are ruining the lives and futures of countless generations of children, are having to maintain to prevent their future global bankruptcy both financial and moral?

It's not listed as a competing interest probably because generally speaking it's not. The funding is already awarded there is no useful influence that GSK could exert on the chair.